Clinical heterogeneity in multiple sclerosis is the rule. Evidence suggests that HLA-DRB1*15 may play a role in clinical outcome. Spinal cord pathology is common and contributes significantly to disability in the disease. The influence of HLA-DRB1*15 on multiple sclerosis spinal cord pathology is unknown. A post-mortem cohort of pathologically confirmed cases with multiple sclerosis (n = 108, 34 males) with fresh frozen material available for genetic analyses and fixed material for pathology was used. HLA-DRB1 alleles were genotyped to select a subset of age- and sex-matched HLA-DRB1*15-positive (n = 21) and negative (n = 26) cases for detailed pathological analyses. For each case, transverse sections from three spinal cord levels (cervical, thoracic and lumbar) were stained for myelin, axons and inflammation. The influence of HLA-DRB1*15 on pathological outcome measures was evaluated. Carriage of HLA-DRB1*15 significantly increased the extent of demyelination (global measure 15+: 23.7% versus 15-: 12.16%, P = 0.004), parenchymal (cervical, P < 0.01; thoracic, P < 0.05; lumbar, P < 0.01) and lesional inflammation (border, P = 0.001; periplaque white matter, P < 0.05) in the multiple sclerosis spinal cord. HLA-DRB1*15 influenced demyelination through controlling the extent of parenchymal inflammation. Meningeal inflammation correlated significantly with small fibre axonal loss in the lumbar spinal cord (r = -0.832, P = 0.003) only in HLA-DRB1*15-positive cases. HLA-DRB1*15 significantly influences pathology in the multiple sclerosis spinal cord. This study casts light on the role of HLA-DRB1*15 in disease outcome and highlights the powerful approach of using microscopic pathology to clarify the way in which genes and clinical phenotypes of neurological diseases are linked.
BACKGROUND:Chlamydia pneumoniae infection has been linked to the development of coronary heart disease (CHD), but its relationship to CHD risk factors is less clear. OBJECTIVE: To determine the relationship between past infection with C. pneumoniae and risk factors for CHD, including body weight amongst subjects with and without CHD. METHODS: Antibodies to C. pneumoniae and a range of CHD risk factors were determined in 170 subjects, of whom 43 had recent onset angina. Anthropometric, haemodynamic, lipid and metabolic measurements were obtained and related to antibody status in univariate and multivariate analyses. RESULTS: IgG seropositive (n ¼ 62) did not differ from seronegative subjects in age but were significantly heavier (26.6 AE 0.4 vs 25.5 AE 0.3 kg=m 2 , P ¼ 0.02). The prevalence of seropositivity was similar for subjects with and without CHD and for those with or without hypertension. Subjects with fasting insulin levels greater and those with LDL diameters below the median also had a significantly higher prevalence of seropositivity (45.3 vs 27.3%, P ¼ 0.015 and 45.0 vs 29.4%, P ¼ 0.045 respectively). However in multivariate analysis only body mass index remained significant (P < 0.05). Results were not explained by differences in socioeconomic class. CONCLUSION: Although the study has failed to find a greater prevalence of antibodies to C. pneumoniae amongst subjects with recent onset angina there were associations with a number of cardiovascular risk factors. An increase in body weight appears to underlie these relationships.
Despite eradication attempts, measles remains a global health concern. Here we report results that demonstrate that a single-dose DNA immunization followed by multiple boosters, delivered orally as a plantderived vaccine, can induce significantly greater quantities of measles virus-neutralizing antibodies than immunization with either DNA or plant-derived vaccines alone. This represents the first demonstration of an enhanced immune response to a prime-boost vaccination strategy combining a DNA vaccine with edible plant technology.
Japanese encephalitis (JE) is a severe disease that is widespread throughout Asia and is spreading beyond its traditional boundaries. Three vaccines are currently in use against JE but only one is available internationally, a mouse-brain-derived inactivated vaccine first used in the 1930s. Although this vaccine has been effective in reducing the incidence of JE, it is relatively expensive and has been linked to severe allergic and neurological reactions. Cell-culture-derived inactivated and attenuated vaccines have been developed but are only used in the People's Republic of China. Other vaccines currently in various stages of development are DNA vaccines, a chimeric yellow fever-JE viral vaccine, virus-like particle vaccines and poxvirus-based vaccines. Poxvirus-based vaccines and the chimeric yellow fever-JE vaccine have been tested in Phase I clinical trials. These new vaccines have the potential to significantly reduce the impact of JE in Asia, particularly if used in an oral vaccine delivery strategy.
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